High protein intake on later outcomes in preterm children: a systematic review and meta-analysis

Abstract

Background: Appropriate protein intake is crucial for growth and development in children born preterm. We assessed the effects of high (HP) versus low protein (LP) intake on neurodevelopment, growth, and biochemical anomalies in these children.

Methods: Randomised and quasi-randomised trials providing protein to children born preterm (<37 completed weeks of gestation) were searched following PRISMA guideline in three databases and four registers (PROSPERO registration CRD42022325659). Random-effects model was used for assessing the effects of HP (≥3.5 g/kg/d) vs. LP (<3.5 g/kg/d).

Results: Data from forty-four studies (n = 5338) showed HP might slightly reduce the chance of survival without neurodisability at ≥12 months (four studies, 1109 children, relative risk [RR] 0.95 [95% CI 0.90, 1.01]; P = 0.13; low certainty evidence) and might increase risk of cognitive impairment at toddler age (two studies; 436 children; RR 1.36 [0.89, 2.09]; P = 0.16; low certainty evidence). At discharge or 36 weeks, HP intake might result in higher weight and greater head circumference z-scores. HP intake probably increased the risk of hypophosphatemia, hypercalcemia, refeeding syndrome and high blood urea, but reduced risk of hyperglycaemia.

Conclusions: HP intake for children born preterm may be harmful for neonatal metabolism and later neurodisability and has few short-term benefits for growth.

Impact statement: Planned high protein intake after birth for infants born preterm might be harmful for survival, neurodisability and metabolism during infancy and did not improve growth after the neonatal period. Protein intake ≥3.5 g/kg/d should not be recommended for children born preterm.

Fig. 1. Flow diagram of study selection.

Flow chart showing the literature identification and selection via databases and registers.

Fig. 2. Forest plots of effects of planned high vs. low protein intake.

Forest plots presenting the effects of planned high vs. low protein intake on a survival without neurodisability at or beyond 12 months, b survival to discharge or till 36–40 weeks, c survival up to infancy, and d survival up to the toddler period. CI confidence interval; M-H Mantel–Haenszel.

Fig. 3. Forest plots of effects of planned high vs. low protein intake.

Forest plots presenting the effects of planned high vs. low protein intake on a neurodisability during the toddler period, b neurodisability in childhood, c cerebral palsy during the toddler period, and d cerebral palsy in childhood. CI confidence interval, M-H Mantel–Haenszel.

Fig. 4. Forest plots of effects of planned high vs. low protein intake.

Forest plots presenting the effects of planned high vs. low protein intake on a cognitive impairment or delay, b language impairment or delay, c motor impairment or delay, and d blindness, and edeafness during the toddler period. CI confidence interval, M-H Mantel–Haenszel.